Activation of D1 dopamine receptors stimulates the release of GABA in the basal ganglia of the rat.
ABSTRACT Here we have explored whether dopamine is able to modulate the release of gamma-aminobutyric acid (GABA) from striatal terminals to substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and caudate-putamen. The type of dopamine receptors involved was assessed by the blocking effect of either SCH 23390 (D1 antagonist) or (-)-sulpiride (D2 antagonist) of the dopamine effect. Dopamine stimulated (EC50 3.2 microM) the depolarization-induced release of [3H]GABA from slices isolated from all of the above mentioned nuclei. SCH 23390 dose-dependently blocked the dopamine stimulation, but (-)-sulpiride did not show any blocking effect. The results suggest that dopamine via D1 receptors modulates the release of GABA from striatal GABAergic terminals.
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ABSTRACT: In striatonigral projections activation of dopamine D3 receptors (D3Rs) potentiates the stimulation of GABA release and cAMP production caused by activation of dopamine D1 receptors (D1Rs). Cytoplasmic [Ca(2+)] in the terminals controls this response by modulating CaMKII, an enzyme that depresses D3R action. To examine the effects of dopamine deprivation on D3R signaling we investigated their function in striatonigral terminals of hemiparkinsonian rats. Denervation switched the signaling cascade initiated by D3R activation. In the non-lesioned side activation of D3R potentiated the stimulatory effects of D1R activation on cAMP production and K(+)-depolarization induced [(3)H] GABA release. In contrast, in the denervated side the stimulatory effects of both D1R activation and forskolin administration were blocked by D3R activation. In non-lesioned slices, D3R responses were inhibited by the activation of CaMKII produced by K(+)-depolarization (via increased Ca(2+) entry). The CaMKII-induced inhibition was blocked by the selective inhibitor KN-62. In denervated tissues the response to D3R stimulation was not modified either by K(+) depolarization or by blocking CaMKII with KN-62. Immunoblotting studies showed that depolarization-induced CaMKII binding to the D3 receptor and CaMKII phosphorylation were suppressed in denervated tissues. We also determined calmodulin expression with PCR and immunoblot techniques. Both techniques showed that calmodulin expression was depressed in the lesioned side. In sum, our studies show that dopaminergic denervation switches the D3R signaling cascade and depresses CaMKII signaling through a process that appears to involve reduced calmodulin levels. Since calmodulin is a major cytoplasmic Ca(2+) buffer our findings suggest that abnormal Ca(2+) buffering may be an important component of the abnormalities observed during dopaminergic denervation. Copyright © 2014. Published by Elsevier Inc.Neurobiology of Disease 12/2014; 74. DOI:10.1016/j.nbd.2014.12.008 · 5.20 Impact Factor
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ABSTRACT: The medial entorhinal cortex (MEC) receives a dense dopaminergic innervation and expresses dopamine receptors. However, little is known about the effect of dopamine on GABAergic transmission in this region of the brain. In this study, we recorded GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) by using whole-cell patch-clamp technique. Application of dopamine at 10 μM and 100 μM significantly increased the frequency and amplitude of sIPSCs. This effect of dopamine is primarily mediated by acting at D1-like dopamine receptors, but not D2-like and α1 adrenergic receptors, since dopamine-induced increased in frequency and amplitude of the sIPSCs was completely blocked by D1-like, but not D2-like or α1 adrenergic, receptor antagonist. However, application of dopamine did not affect the frequency and amplitude of the mIPSCs, implying that the effect of dopamine on the GABAergic transmission is action potential-dependent. Together, these findings reveal an indirect mechanism by which activation of D1-like receptors could inhibit the excitability of layer III pyramidal neurons in the MEC.